According to FDA guidelines as listed in 21CFR 314.94 (a)(9)(iv), generic drug products must demonstrate pharmaceutical equivalence and bioequivalence to the reference listed drug (RLD) to gain FDA approval. For generic ophthalmic solutions that are qualitatively (Q1) and quantitatively (Q2) the same as the RLD, bioequivalence is considered to be self-evident and a waiver for in vivo studies can be requested. Unlike solutions, ophthalmic suspensions/emulsions require an additional step of dissolution or release before the drug is absorbed from the dosage form. Pharmaceutically equivalent suspensions or emulsions can have varying physicochemical properties either because of the differences introduced during manufacturing or formulation, which in turn may affect precorneal residence time, drug release, and ocular bioavailability. Therefore, FDA guidelines recommend that ophthalmic dosage forms such as suspensions and emulsions that are Q1 and Q2 the same as the RLD, bioequivalence must be demonstrated. However, there is sparse literature explaining how the differences in physicochemical properties of ophthalmic suspensions/emulsions result in differences in ocular bioavailability. Moreover, suitable bioequivalence methods are lacking for studying generic ophthalmic suspensions and emulsions. An investigation of the relationship between physicochemical properties and their effect on ocular bioavailability is crucial to formulate suspensions/emulsions that are both pharmaceutically equivalent and bioequivalent. We hypothesize that key physicochemical properties such as particle/globule size, size distribution, viscosity, pH, and zeta potential can influence drug release, residence time, and stability of the suspensions or emulsions, and hence, bioavailability. To address this hypothesis, we will manufacture corticosteroid suspension and emulsion formulations with different physicochemical properties and assess their drug release, stability, and ex vivo delivery. Based on these studies, we will identify stable formulations and key physicochemical properties that result in significant differences in release and/or ex vivo topical ocular delivery. A physicochemical property that shows maximum differences in drug release and/or ex vivo delivery for each the suspension/emulsion formulations will be identified and assessed for in vivo precorneal residence and ocular bioavailability in rabbits. We will employ a statistical model for population pharmacokinetic analyses to calculate the bioequivalence of suspensions and emulsions. Through collaborative consultations with FDA counterparts that allow optimal design of studies, this project will identify key physicochemical properties of Q1 and Q2 suspension/emulsion dosage forms that alter ocular drug bioavailability. The findings of this project would lay a foundation for developing guidelines for conducting bioequivalence studies for generic ophthalmic suspensions and emulsions.